14,15-dihydroxyeicosatrienoic acid (DHET) potentiates bradykinm-mduced relaxation of porcine coronary arteries

DHETs are potent coronary vasodilators formed from epoxyeicosatrienoic acids (EETs), cytochrome P450 epoxygenase metabolites of arachidonic acid (AA). DHETs can be taken up by endothelial (endo) cells and incorporated into phospholipids that participate in cell signal transduction. However, the functional significance of DHET incorporation into endo cell lipids is unknown. We examined relaxation to bradykinin (BK), a potent stimulator of endo phospholipid hydrolysis, before (control) and after (post DHET) incubation with 14,15-DHET In porcine coronary artery (PCA) rings submaximally contracted with a thromboxane mimetic, U46619, 14,15-DHET (0.1-5 μM) produced sustained relaxation (59 ± 9% [mean±SE] at 5 μM); whereas relaxation to BK (0.3-100 nM) was transient. After 30 min incubation with 14,15-DHET (5 μM), BK-induced relaxation was potentiated in both magnitude (table) and duration. Pretreatment with 2 μM triacsin C (an inhibitor of acyl-CoA synthases), which blocked [³H]AA incorporation into endo cell lipids and PCA rings, blocked 14,15-DHET-induced potentiation of relaxation to BK. We conclude that incorporation of 14,15-DHET into cell lipids results in potentiation of BK-induced relaxation, providing the first evidence that DHETs incorporated into cell lipids are capable of altering cellular function. BK concentration (nM) %relaxation to BK 1 3 10 30 100 control 11±8 39±11 55±10 65±9 77±8 post DHET 39±13*81±9*92±7*92±7 *92±7**p<0.05.